The following facts are known with regard to the medical care-related use of transglutaminase. Firstly, Japanese Patent Application Laid-Open (Kokai) No. Sho 62-74360 discloses an artificial skin which contains as a component a membrane made of crosslinked protein and/or peptide with action of transglutaminase, and this artificial skin is possessed of high biological compatibility, because not only it is excellent in its tensile strength, elongation, flexibility and oxygen permeability but also it has excellent water vapor permeability. Also, Japanese Patent Application Laid-Open (Kokai) No. Hei 2-108631 discloses an immunosuppressive agent which contains transglutaminase as the active ingredient, but the disclosure is limited to in vitro experiments and immunological discussions and is not even suggestive of actual wound healing in vivo. In addition, as will be described later, such use of transglutaminase is evidently different from that of the present invention.
As for wound healing, post-disinfection primary suture and the like treatments are generally carried out, which essentially require surgical operation. However, it is difficult to apply surgical suture to a wound having large skin damage, as well as burn injury and the like.
On the other hand, it is extremely important in the case of wound healing to treat the wound without leaving a scar behind, not only from organic and functional points of view but also from a cosmetic point of view.
Skin grafting, redressing appliance application, pharmacotherapy, radiotherapy and the like are generally employed in order to prevent such a cicatricial contracture, but each means has its own drawbacks. That is, in the case of skin grafting, several problems have been pointed out which include not only a necessity of carrying out surgical treatments, but also a difficulty in carrying out ideal skin grafting when a wound covers a wide area like in the case of heavy burn injury because of extreme limitation in obtaining the donor skin, and a wound contraction which does not stop immediately after the skin grafting but continues for a considerably prolonged period of time on the interface between the grafted skin and the wound surface, the skin graft suture line and the like. As to the use of a redressing appliance, notwithstanding such use is an auxiliary means and such appliance needs a long-time application accordingly, some problems have been pointed out in that such appliance cannot actually be used for a prolonged period of time required for the treatment. With regard to pharmacotherapy, distinct effects cannot be expected from steroid ointments, and only an auxiliary effect can be expected from tranilast which has a function to inhibit degranulation of mast cells. Though radiotherapy can repress wound contraction, it has a drawback in that it inhibits healing of wounds.
Several wound protectives have also been proposed and put into practical use, but each has its own problems. That is, in the case of a lyophilized porcine skin, re-covering is required because such a skin melts on the wound surface, and it also requires regeneration with physiological saline prior to its use. An artificial skin made of collagen sometimes causes a slight pain and an uncomfortable feeling. A plasma membrane and a fibrin membrane made from human blood are not capable of fully discharging exudate when the wound surface is secretory, and the supply of these membranes is limited because of the use of human blood as a raw material. In addition, pains and uncomfortable feelings at the time of application are commonly seen in all these wound protectives. What is more, all these wound protectives are not sufficiently possessed of functions necessary for the treatment process, in terms of drying of the affected part, stanching of blood, prevention of infection and the like.
As hemostatic agents, gelatin, fine fibrous collagen, thrombin and the like are indeed known, but with increasing demand for the development of more excellent agents.